TY - JOUR
T1 - Pathophysiological significance of the obese gene product, leptin, in ventromedial hypothalamus (VMH)lesioned rats
T2 - Evidence for loss of its satiety effect in VMH-lesioned rats
AU - Satoh, Noriko
AU - Ogawa, Yoshihiro
AU - Katsuura, Goro
AU - Tsuji, Tetsuo
AU - Masuzaki, Hiroaki
AU - Hiraoka, Junko
AU - Okazaki, Taku
AU - Tamaki, Mikio
AU - Hayase, Minoru
AU - Yoshimasa, Yasunao
AU - Nishi, Shigeo
AU - Hosoda, Kiminori
AU - Nakao, Kazuwa
PY - 1997
Y1 - 1997
N2 - To explore the pathophysiological significance of the obese (ob) gene product, leptin, in ventromedial hypothalamus (VMH)-lesioned rats, we examined the synthesis and secretion of leptin and its satiety effect in VMH- lesioned rats compared with those in sham-operated rats. Northern blot analysis revealed that ob gene expression is markedly augmented in the mesenteric and sc white adipose tissue, but remained unchanged in the epididymal white adipose tissue during the development of obesity in VMH- lesioned rats. Plasma leptin levels were relatively constant in sham-operated rats, but were elevated during the development of obesity in VMH-lesioned rats. In sham-operated rats, a single iv (1.0 mg/rat) or intracerebroventricular (2.0 μg/rat) injection of recombinant human leptin reduced food intake and body weight gain in sham-operated rats. By contrast, no significant effect on food intake or body weight gain was observed in VMH- lesioned rats. The present study provides evidence that VMH-lesioned rats overproduce leptin and increase its release but cannot respond to it and suggests that the loss of its satiety effect contributes to the development of obesity and the obesity-related phenotypes in VMH-lesioned rats.
AB - To explore the pathophysiological significance of the obese (ob) gene product, leptin, in ventromedial hypothalamus (VMH)-lesioned rats, we examined the synthesis and secretion of leptin and its satiety effect in VMH- lesioned rats compared with those in sham-operated rats. Northern blot analysis revealed that ob gene expression is markedly augmented in the mesenteric and sc white adipose tissue, but remained unchanged in the epididymal white adipose tissue during the development of obesity in VMH- lesioned rats. Plasma leptin levels were relatively constant in sham-operated rats, but were elevated during the development of obesity in VMH-lesioned rats. In sham-operated rats, a single iv (1.0 mg/rat) or intracerebroventricular (2.0 μg/rat) injection of recombinant human leptin reduced food intake and body weight gain in sham-operated rats. By contrast, no significant effect on food intake or body weight gain was observed in VMH- lesioned rats. The present study provides evidence that VMH-lesioned rats overproduce leptin and increase its release but cannot respond to it and suggests that the loss of its satiety effect contributes to the development of obesity and the obesity-related phenotypes in VMH-lesioned rats.
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U2 - 10.1210/endo.138.3.4989
DO - 10.1210/endo.138.3.4989
M3 - Article
C2 - 9048594
AN - SCOPUS:8044227781
SN - 0013-7227
VL - 138
SP - 947
EP - 954
JO - Endocrinology
JF - Endocrinology
IS - 3
ER -
